Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DCs) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute illness to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage-HLADR+ cells lacking DC markers. Increased frequency of CD163+ CD14+ cells within the recently discovered DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of programmed death-ligand 1 (PD-L1) in conventional DCs (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naïve CD4+ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.
FörderungenWilhelm Sander Stiftung Bavarian Elite Graduate Training Network Villigst Foundation Bavarian State Ministry of Science and the Arts Else-Kroner-FreseniusStiftung Germany's Excellence Strategy EXC2151 'Deutsche Forschungsgemeinschaft' Faculty of Medicine of the LMU Munchen Free State of Bavaria under the Excellence Strategy of the Federal Government and the States LMUexcellent Federal Ministry of Education and Research (BMBF) initiative "NaFoUniMedCovid19" Federal Ministry of Education and Research (BMBF) initiative "COMBAT C19IR" Deutsche Forschungsgemeinschaft